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- Andréasson, Sten, et al.
(författare)
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Clinical studies of X-linked retinitis pigmentosa in three Swedish families with newly identified mutations in the RP2 and RPGR-ORF15 genes
- 2003
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Ingår i: Ophthalmic Genetics. - : Swets & Zeitlinger Publishers. - 1381-6810 .- 1744-5094. ; 24:4, s. 215-223
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To describe new disease-causing RP2 and RPGR-ORF15 mutations and their corresponding clinical phenotypes in Swedish families with X-linked retinitis pigmentosa (XLRP) and to establish genotype-phenotype correlations by studying the clinical spectrum of disease in families with a known molecular defect. Methods: Seventeen unrelated families with RP and an apparent X-linked pattern of disease inheritance were identified from the Swedish RP registry and screened for mutations in the RP2 and RPGR (for the RP3 disease) genes. These families had been previously screened for the RPGR exons 1-19, and disease-causing mutations were identified in four of them. In the remaining 13 families, we sequenced the RP2 gene and the newly discovered RPGR-ORF exon. Detailed clinical evaluations were then obtained from individuals in the three families with identified mutations. Results: Mutations in RP2 and RPGR-ORF15 were identified in three of the 13 families. Clinical evaluations of affected males and carrier females demonstrated varying degrees of retinal dysfunction and visual handicap, with early onset and severe disease in the families with mutations in the ORF15 exon of the RPGR gene. Conclusions: A total of seven mutations in the RP2 and RPGR genes have been discovered so far in Swedish XLRP families. All affected individuals express a severe form of retinal degeneration with visual handicap early in life, although the degree of retinal dysfunction varies both in hemizygous male patients and in heterozygous carrier females. Retinal disease phenotypes in patients with mutations in the RPGR-ORF15 were more severe than in patients with mutations in RP2 or other regions of the RPGR.
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| 2. |
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| 3. |
- Eksandh, Louise
(författare)
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Clinical expressions of juvenile hereditary retinal degenerations and macular dystrophies: Electrophysiological and genetic studies
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hereditary retinal degenerations are the most frequent reason for severe visual handicap among young people in Scandinavia today. In the six papers included in this thesis the phenotypic expressions, with emphasis on the electrophysiological findings, of five different juvenile hereditary retinal degenerations are described. The diagnoses have been confirmed by genetic analysis. The retinal disorders presented are all caused by mutations in genes identified during the last six years. Patients with Best disease and three defined mutations (T357C, T130C and C416A) in the VMD2 gene demonstrated a variable, but moderate visual acuity reduction presenting in childhood, atrophic changes in the macula and pathological results of the EOGs. Patients with the new mutation T370C in VMD2 demonstrated an atypical phenotype with mostly a late onset of visual failure. Batten disease patients, both homozygous and compound heterozygous for the 1.02 kb deletion in the CLN3 gene, presented a severe, widespread retinal degeneration, which could be confirmed by full-field ERG. However, in the patients heterozygous for this deletion the onset of visual failure and the disease progression in terms of other symptoms was delayed. 30 patients with Juvenile X-linked retinoschisis and seven different mutations in XLRS1 presented a wide variability in the phenotype between, as well as within, families with different genotypes, suggesting that additional factors may contribute to the disease severity. Full-field ERG is an important diagnostic tool in confirming the diagnosis in this disorder. Two pairs of siblings with Stargardt disease, diagnosis confirmed by genetic linkage to the ABCA4 gene region, presented two different clinical expressions of the disease regarding the distribution of the retinal dysfunction, which could be confirmed by full-field ERGs and MERGs. Ten patients with Rodmonochromacy and different mutations in the CNGA/CNGB3 genes presented a similar clinical phenotype, confirming the essential function of both the a- and the b-subunit of the cGMP-gated cation channel in cone photoreceptor function.
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| 4. |
- Eksandh, Louise, et al.
(författare)
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Clinical features of achromatopsia in Swedish patients with defined genotypes.
- 2002
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Ingår i: Ophthalmic Genetics. - : Swets & Zeitlinger Publishers. - 1744-5094 .- 1381-6810. ; 23:2, s. 20-109
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To describe the clinical phenotype, with emphasis on the electrophysiological findings, of patients with autosomal recessive rod monochromacy (RM) and defined mutations in the CNGA3/CNGB3 genes. Methods: RM patients from eight different families were included in the study. Their genotypes were determined by DNA sequencing and/or RFLP analysis of PCR-amplified genomic segments of the CNGA3 and CNGB3 genes. For comparison, we investigated one patient with blue-cone monochromacy (BCM). The clinical examination included best-corrected visual acuity, fundus examination, and full-field ERG. In six patients, the examination was complemented by multifocal ERG (MERG). Results: Three patients had three different CNG3A genotypes. Five patients were homozygous and one patient compound heterozygous for a 1-bp deletion (1148delC) in the CNGB3 gene. All patients examined presented with a visual acuity of 0.1-0.15. Small residual cone responses were noted in four young RM patients. The oldest patient examined (age 47 years) presented with pigmentary changes in the mid-peripheral retina and concentric constrictions of the visual fields. Conclusions: Patients with RM and mutations in the CNGA3/CNGB3 genes presented a similar clinical phenotype, confirming the essential function of both the alpha- and beta-subunits of the cGMP-gated cation channel in cone photoreceptor function. Small remaining cone responses in a few of the younger patients and mid-peripheral pigmentary degenerations in the oldest patient examined indicate that there could be some degree of progression in retinal dysfunction in at least some patients with RM.
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| 5. |
- Eksandh, Louise, et al.
(författare)
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Different clinical expressions in two families with Stargardt's macular dystrophy (STGD1)
- 2001
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Ingår i: Acta Ophthalmologica Scandinavica. - : Wiley. - 1395-3907. ; 79:5, s. 524-530
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To describe the clinical expressions, with emphasis on electrophysiological examinations, in two Swedish families with Stargardt's macular dystrophy (STGD1). Methods. Two pairs of siblings with STGD1, for whom diagnosis had been confirmed by genetic linkage to the ABCA4 gene region, were examined regarding visual acuity, kinetic perimetry, fundus photography, full-field ERG and multifocal ERG (MERG). Possible disease-causing mutations were screened for by DNA sequencing of selected regions of the ABCA4 gene. Results. All STGD1 patients, had visual acuity 0.07-0.1. The two families presented different fundus appearances, MERGs and implicit times on. 30 Hz flicker white light full-field ERGs. Genetic analysis revealed one unique sequence variation in exon 19 of the ABCA4 gene, in one allele from the patients of one of the families. This point mutation causes the amino acid substitution T972N in the ABCR protein. Conclusion. Two pairs of siblings with STGD1 presented two different expressions of the disease regarding the distribution of the retinal dysfunction. One possible molecular explanation to the different clinical expressions may be the T972N substitution present in the ABCR protein in one of the STGD1 families investigated.
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| 6. |
- Eksandh, Louise, et al.
(författare)
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Full-field ERG in patients with Batten/Spielmeyer-Vogt disease caused by mutations in the CLN3 gene.
- 2000
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Ingår i: Ophthalmic genetics. - 1381-6810. ; 21:2, s. 69-77
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To investigate, using full-field ERG, the retinal function in patients with Batten/Spielmeyer-Vogt disease caused by mutations in the CLN(3) gene. METHODS: Batten disease status of five patients was confirmed by the presence of vacuolated lymphocytes in peripheral blood and the identification of mutations in the Batten disease gene (CLN(3)). Visual acuity, fundus appearance, and full-field ERG were examined in all patients (age 4-19 years). The examination was repeated in one patient after 16 months. RESULTS: Three unrelated patients were homozygous for the most common mutation in CLN(3), the 1.02 kb deletion; two patients (sisters) were heterozygous for the 1.02 kb deletion and an as yet unidentified mutation in the CLN(3) gene. Full-field ERG recordings in all five patients demonstrated no rod responses and only small remaining cone responses, which could be detected with 30 Hz-flicker stimulation. Re-examination of a six-year-old girl after 16 months revealed a fast progression of the retinal degeneration. CONCLUSION: Full-field ERG recordings in Batten disease patients, both homozygous and heterozygous for the 1.02 kb deletion in the CLN( 3) gene, confirm retinal degeneration to be severe, widespread, and with a rapid progression early in the disease course. The onset of visual failure may be delayed when compared to the classic disease course, particularly in patients who are not homozygous for the most common CLN(3) mutation, a 1.02 kb deletion. In that case, the disease progression in terms of other symptoms may also be further delayed.
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| 7. |
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| 8. |
- Schatz, Patrik, et al.
(författare)
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Macular appearance by means of OCT and electrophysiology in members of two families with different mutations in RDS (the peripherin/RDS gene).
- 2003
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Ingår i: Acta Ophthalmologica Scandinavica. - : Wiley. - 1395-3907. ; 81:5, s. 500-507
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To describe the phenotype using electroretinography and optical coherence tomography (OCT) in members of two families with different mutations in RDS. Methods: DNA was extracted from blood samples and used for mutation screening by denaturing gradient gel electrophoresis (DGGE) and nucleotide sequencing of RDS exons. Patients were examined with clinical evaluation, full-field electroretinography (ERG), multifocal electroretinography (mfERG) and OCT. Results: An Arg-46 stop codon conversion and a Ser-125 Leu substitution were found, respectively, in affected members of the two families. Phenotypes included retinitis pigmentosa, central areolar choroidal dystrophy, macular dystrophy and adult vitelliform maculopathy. The vitelliform lesion was clearly delineated on OCT, but mfERG showed preserved function. Optical coherence tomography showed attenuation of retinal reflectivity in two cases. Conclusion: By combining traditional investigations with mfERG and OCT, we were able to obtain a more refined evaluation of contributing macular and generalized retinal dysfunction, respectively, in patients with hereditary retinal disease.
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